Upendra K. Pandit

A facile transformation of sugar lactones to azasugars

Abstract The synthesis of pyrano- and furano- sugar lactams from the corresponding lactones, in a five step sequence, is described.

The first synthesis of the ABCD ring system of manzamine A. Construction of the macrocyclic ring D.

The synthesis of the ABCD ring system of manzamine A has been achieved using the olefin metathesis cyclization reaction for the crucial macrocyclic ring D formation step.

A formal synthesis of castanospermine using an olefin metathesis cyclisation reaction as a key step

Abstract The formal synthesis of castanospermine (1) starting from tetrabenzylgluconolactam (3) is described. Olefin metathesis cyclisation reaction of dialkene 9, derived from 3, leads to indolizidinone 10, which can be used as a key intermediate for the synthesis of castanospermine (1) and its analogues.

SYNTHESIS MEDIATED BY RING-CLOSING METATHESIS : APPLICATIONS IN THE SYNTHESIS OF AZASUGARS AND ALKALOIDS

The application of the ring-closing metathesis (RCM) reaction to the construction of a wide variety of nitrogen-containing ring systems is described. The examples include pyrrolizidine, indolizidine, and quinolizidine derivatives related to azasugars. A formal total synthesis of castanospermine (5) is presented. The utilisation of two RCM steps in the synthetic sequence leading to the multicyclic ABCDE nucleus 7 of the complex alkaloid manzamine A (6) is discussed.

On the question of one-electron transfer in the mechanism of reduction by nadh-models

Abstract The fluorescence of 1-benzyl-1,4-dihydronicotinamide (BNAH) is quenched by a variety of electron acceptors. The dependence of the rate constant of the quenching process on the electrochemical reduction potentials of the quenchers corresponds with that expected for quenching by an electron transfer mechanism in which BNAH acts as an electron donor with a one electron oxidation potential of 0.76 ± 0.02 V (in acetonitrile relative to the saturated calomel electrode). From this oxidation potential, and the reduction potentials of a number of substrates reported to be reduced by BNAH, the rates of thermal one-electron transfer from BNAH to these substrates were estimated via the Rehm-Weller relation for outersphere one-electron transfer. These calculated rates are many orders of magnitude lower than experimental rates reported for the overall reduction processes. This seems to exclude outersphere one-electron transfer as an intermediate step in such reductions.

Synthesis of the homochiral “tricyclic heart” of manzamine A

Abstract An expedient and enantiospecific synthesis of a strategically functionalized tricyclic intermediate for the construction of manzamine A is described.

Unconventional nucleotide analogues—I : N9-purinyl α-amino acids

Abstract Reaction of 6-chloropurine ( 3 ), 2,6-dichloropurine ( 4 ) and 2-amino-6-chloropurine ( 5 ) with t-butyl α-benzyloxycarbonylamido-γ-bromobutyrate ( 6b ) gave high yields of the corresponding N 6 -alkylated products ( 10a , 11a , 12a ). Suitable transformations of the latter led to the formation of 4-(N 9 -purinyl)-α-aminobutyricacids correspon xanthine ( 23 ).Abstract Reaction of 6-chloropurine ( 3 ), 2,6-dichloropurine ( 4 ) and 2-amino-6-chloropurine ( 5 ) with t-butyl α-benzyloxycarbonylamido-γ-bromobutyrate ( 6b ) gave high yields of the corresponding N 6 -alkylated products ( 10a , 11a , 12a ). Suitable transformations of the latter led to the formation of 4-(N 9 -purinyl)-α-aminobutyricacids correspon xanthine ( 23 ).

Models of folate coenzymes. VII: Synthesis and carbon transfer reactions of N5,N10-methenyl and N5,N10-methylenetetrahydrofolate models

Abstract Carboxylate esters react with 1,2-diaminoethanes to yield imidazolines, which upon consecutive reaction with acetic anhydride or tosyl chloride and methyl iodide give imidazolinium salts that serve as models of N5,N10-(CH+)-tetrahydrofolate (THF) coenzymes (7a, b and 18a, b). Reduction of the latter salts with sodium borohydride or reaction with anions (R−) give the corresponding 5,10-[CH(H,R)]-THF models. Mono- and bifunctional nucleophiles react with 18a, b to yield carbon-transfer products 6-Alkylamino-1,3-dimethyluracils react with 1 tosyl-3,4,4-trimethylimidazolidine (the reduction product of 18b), in the presence of acetic acid, to form carbon transfer products via a mechanism which bears close analogy to the mechanism of action of thymidylate synthetase.

RING-CLOSING METATHESIS MEDIATED SYNTHESIS OF PYRROLIZIDINE AND QUINOLIZIDINE AZASUGARS

Abstract The synthesis of a novel perbenzylated pyrrolizidine starting from 2,3,5-tri- O -benzyl-arabinofuranose and based on a ring-closing metathesis (RCM) reaction is presented. In an analogous procedure, 2,3,5-tri- O -benzylxylopyranose was converted into a hitherto unprecedented quinolizidine azasugar.

NAD(P)H Models 201: Chemoselective metal ion catalyzed reduction of α-keto-β,γ-unsaturated esters by 1,4-dihydropyridine derivatives

Abstract Ethyl 2-oxo-4-aryl-3-butene-1-oates 1a – 1c are reduced by NAD(P)H models (1-n-propyl-1,4-dihydronicotinamide ( 4 ) and Hantzsch ester( 5 )), in presence of magnesium perchlorate. One equivalent of the reductant reduces the substrates selectively to the corresponding 2-oxo-4-arylbutanoates ( 6 , 10a , b ). An additional equivalent and higher temperature, converts ethyl 2-oxo-4-phenylbutanoate ( 6 ) to ethyl 2-hydroxy-4-phenylbutanoate ( 7 ). Reduction of ethyl 2-oxo-4-phenyl-3-buten-1-oate ( 1a ) by Hantzsch ester in C 2 H 5 OD or by Hantzsch ester-4,4-d 2 in C 2 H 5 OH, leads to direct transfer of the hydrogen or deuterium, respectively, without isotopic scrambling. These results have been interpreted to support the hydride transfer mechanism.